Graduate medical training.
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Biomedical subjects
Publications and source records attributed to L I Mann.
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The longitudinal hemodynamic response of the uterine circulation to pregnancy and to repetitive embolic insult was assessed in 23 singleton ewe pregnancies by means of electromagnetic flow transducers and radionuclide-labeled microspheres. The data indicate that the longitudinal hemodynamic changes observed in the uterine circulation were directly related to the growth rate of the tissue which it supplied. The hemodynamic impact of embolization appears to be secondary to its impact on tissue growth. Embolization simply blunts the normal incremental increases in uterine perfusion and the cross-sectional area of the uterine vascular bed. It alters actual tissue perfusion only within a portion of the cotyledonary circulation. Finally, the data support the presence of functional arterial anastomoses between the two sides of the uterine circulation in this species.
In the chronic pregnant ewe preparation, daily blood samples, for the determination of plasma cortisol and progesterone levels by specific radioimmunoassay, were obtained from the fetal distal aorta, uterine vein, and uterine artery prior to, during, and after repetitive embolization of the uterine circulation with 15 mu microspheres. A significant increase in fetal cortisol was observed in all animals during the first 3 days of embolization. In those which subsequently entered premature labor, this increase was progressive and was associated with a fall in the uterine venous progesterone level but was unrelated to changes in either the maternal cortisol level or fetal physiologic parameters. In animals which did not enter premature labor, progesterone levels in the uterine vein and estimated progesterone release rates were elevated with an accentuated peak-trough pattern during the postembolization period. In these animals fetal cortisol returned to control levels. The data suggest that cortisol and progesterone biosynthesis within the fetoplacental unit is altered by microembolic placental damage.
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In this study we examined the relationship between fetal metabolism, cardiovascular function, brain function, and eventual neuropathological outcome in the last third of gestation in the chronic fetal lamb preparation under a variety of environmental conditions. We concluded that the progressive hypoxia and metabolic acidosis secondary to acute placental insufficiency result in cerebral damage and functional deficit. Growth retardation and its attendant chronic hypoxemia, secondary to chronic placental insufficiency, do not have these results. However, intermittent interference with the umbilical circulation is associated with both functional and structural evidence of cerebral damage without systemic metabolic abnormality. The experimental, physiologic, and clinical implications of these observations are discussed.
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The fetal metabolic response to repetitive placental damage, produced by microsphere embolization of the uteroplacental circulation, was examined longitudinally in eight singleton fetal lambs and compared with similar data from seven controls. Significant morphometric fetal growth retardation was associated with an abrupt cessation of the normal increases in oxygen, glucose, and lactate uptake observed in the control animals. However, fetal blood levels and umbilical substrate quotients did not change. At the time of sacrifice, fetal oxidative metabolic rate was reduced significantly. The significance of these findings relative to intact fetal survival is discussed.
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The uptake of meperidine by the brain of the fetal lamb was investigated by determining the concentration of meperidine in the fetal brachiocephalic artery and sagittal vein after intravenous and intramuscular administration to the mother. A positive arteriovenous gradient across the fetal brain existed for 10 minutes after intravenous administration, and for 20 to 25 minutes after intramuscular administration, thus indicating the uptake of meperidine by the fetal brain. The peak concentration of unbound meperidine in the fetal brain, as estimated from the plasma concentration of free meperidine at equilibrium, was three to four times greater after intravenous administration than after intramuscular administration. The findings suggest that, during labor, the route of administration of meperidine will determine the time course of meperidine in the fetal brain and, consequently, the time action of effects seen in the neonate. The lag time required for plasma-brain equilibration may explain the lack of correlation between the incidence of neonatal respiratory depression and the levels of meperidine in the cord after intramuscular administration.
The uterine and umbilical blood flow response to uteroplacental insufficiency, produced by microsphere embolization of the uteroplacental circulation, was examined by means of electromagnetic flow transducers in 12 pregnant ewes. No acute changes were observed in either circulation immediately after embolization of the uterine vasculature. Significant morphometric fetal growth retardation, in terms of weight, length, and ponderal index, was not associated with early changes in fetal pH, PO2, or PCO2. However, the incremental increases in both flows that were observed in control animals did not occur either during or after embolization because of an increase in vascular resistance. During and after embolization the incremental increase in uterine blood flow was blunted or decreased in most, but not all, animals. A rapid, progressive, and persistent decrease in umbilical flow occurred in the growth-retarded group. The significance of these findings relative to intrauterine growth is discussed.
The relationship between fetal electrocortical activity and multiple fetal parameters was examined in chronically instrumented fetal lambs. Consistent small but significant changes in fetal heart rate, mean arterial pressure, umbilical blood flow, and the cerebral uptake of glucose relative to oxygen were observed as fetal electrocortical activity cyclically shifted between high-voltage slow activity and low-voltage fast activity. Cardiovascular parameters were higher and the cerebral uptake of glucose relative to oxygen was lower during high-voltage slow activity than during low-voltage fast activity. The implication of these observations is discussed.
The role of antibody, interferon, and cell-mediated immunity (CMI) were studied to determine the mechanisms for progesterone enhancement of vaginal herpes simplex virus type 2 (HSV 2) infection in mice. Three groups of mice were studied: nonpregnant control, pregnant, and nonpregnant progesterone-treated mice. Vaginal infection with HSV 2 did not elicit a neutralizing antibody or a systemic interferon response in any of the groups tested. Splenic lymphocytes from noninfected and infected mice were stimulated in vitro with a nonspecific T-cell mitogen concanavalin (Con A) to measure the proliferative phase of CMI in these groups of mice. No suppression of (3H) thymidine (3HTdR) uptake was found in the pregnant or nonpregnant, progesterone-treated animals as compared to nonpregnant control mice. When progesterone was added directly to the splenic lymphocytes and continuously present during Con A stimulation a statistically significant depression of 3HTdR incorporation was found. We concluded that progesterone depresses Con A stimulation of murine lymphocytes, but progesterone must be continuously present to do so.
The effect of total cord occlusion (TCO) on the time sequence of fetal oxygenation, metabolic and cardiovascular parameters and on brain function of the sheep fetus was studied. It was also of importance to differentiate between cardiovascular alteration following TCO due to hypoxia and baroreceptor response, respectively. The investigations were performed on 11 near term pregnant sheep with dated gestational age of 126--137 days. Catheters were placed in the fetal aorta for monitoring fetal arterial blood pressure (FA BP), fetal heart rate (FHR). Blood samples were drawn and analysed for pH, PCO2 and SO2. An electromagnetic flow probe was placed around the common umbilical vein. Fetal EEG was measured over the right hemisphere. All parameters were studied over a varying time of TCO.
We have determined the renal clearance of meperidine and inulin simultaneously under steady-state conditions by using the chronic fetal lamb preparation. Meperidine was infused at a constant rate of 3.2 mg/min into the maternal vena cava, and [14C]inulin was infused at a constant rate of 0.22 muCi/min into the fetal vena cava. Total fetal urine output was collected for three consecutive 15-min intervals, and fetal blood was sampled at the midpoint of each urine collection. The mean meperidine clearance in 12 studies was 12.04 +/- 2.90 (S.E.) ml/min, whereas mean inulin clearance was 2.48 +/- 0.35 (S.E.) ml/min. In all but one animal, the ratio of meperidine clearance to inulin clearance is greater than one, indicating tubular secretion of meperidine. The results show that there is a negative relationship between meperidine clearance and urine pH, but there is no relationship between meperidine clearance and gestational age or urine flow rate. These results suggest that meperidine is secreted across the renal tubules by "ion trapping."
Total cesarean section rates and rates of various indications for primary cesarean section were reviewed for four yearly periods during the past decade. The time periods studied were chosen to follow the introduction of new obstetric practices and technologic advances in monitoring fetal condition. The total cesarean section rate increased from 6.8% to 17.1% during this time. The most common indication for primary cesarean section was cephalopelvic disproportion, which represented approximately 40% of cases during each study period. Primary cesarean section for fetal distress increased to 28.2% but has decreased over the past 2 years to a present rate of 11.7%. Primary cesarean section for breech presentation increased from 12.3% to 21%. From the perspective of this review a total cesarean section rate of 15% is predicted for the future.
Retrospective review of 457 breech deliveries failed to reveal a significant improvement in neonatal mortality and morbidity rates for those delivered by cesarean section vs. vaginal delivery. A slight but insignificant improvement in salvage was found for the 1,000 to 1,500 gram weight category when delivery was by cesarean section. Most of the deaths in the less than 1,500 gram breech presentation were associated with hyaline membrane disease or congenital defects incompatible with life and sepsis rather than directly related to the manner of breech delivery.